We conducted a genome-wide association study (GWAS) of anorexia nervosa (AN) using a stringently defined phenotype. Analysis of phenotypic variability led to the identification of a specific genetic risk factor that approached genome-wide significance (rs929626 in EBF1 (Early B-Cell Factor 1); P = 2.04 × 10-7; OR = 0.7; 95% confidence interval (CI) = 0.61-0.8) with independent replication (P = 0.04), suggesting a variant-mediated dysregulation of leptin signaling may play a role in AN. Multiple SNPs in LD with the variant support the nominal association. This demonstrates that although the clinical and etiologic heterogeneity of AN is universally recognized, further careful sub-typing of cases may provide more precise genomic signals. In this study, through a refinement of the phenotype spectrum of AN, we present a replicable GWAS signal that is nominally associated with AN, highlighting a potentially important candidate locus for further investigation.

译文

我们使用严格定义的表型对神经性厌食症 (AN) 进行了全基因组关联研究 (gwa)。表型变异性的分析导致鉴定出一种特定的遗传危险因素,该因素具有全基因组意义 (EBF1中的rs929626 (早期b细胞因子1); P   =   2.04  ×   10-7; Or   =   0.7; 95% 置信区间 (CI)  =   0.61-0.8) 与独立复制 (p   =   0.04),提示一个变异介导的瘦素信号失调可能在AN中起作用。具有变体的LD中的多个snp支持名义上的关联。这表明,尽管AN的临床和病因学异质性已得到普遍认可,但对病例的进一步仔细分类可能会提供更精确的基因组信号。在这项研究中,通过改进AN的表型谱,我们提出了名义上与AN相关的可复制gwa信号,突出了潜在的重要候选基因座,以供进一步研究。

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